We propose to develop and demonstrate a novel microfluidic device and assay for selection and optimization of drug delivery vehicles, specifically non-viral vectors for drug delivery to tumors. Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A primary factor is tumor microvasculature with complex effects including convective blood transport, high interstitial pressure and enhanced vascular permeability due to "leaky vessels". Current in-vitro models of tumor drug delivery are oversimplified and, as a result, overestimate in-vivo performance with very poor predictability. We propose to develop a novel microfluidic device that accurately models the tumor microenvironment, with physiologically and morphologically accurate microvasculature including leaky endothelial layers along with 3D solid tumors. This device will allow real-time, quantitative assessment of the performance of delivery vehicles under in-vivo like conditions. In Phase I, we will design and fabricate prototypes of plastic microfluidic chips with embedded microvascular networks. Endothelial cells and tumor cells will be cultured in these networks. The potential of this device in quantifying delivery will be assessed using two well-characterized polymers (one in clinical studies for ovarian cancer therapy). Planned Phase II enhancements include tumor-specific microvasculature and optimized methods for culturing tumor cells with endothelial cells in presence of stromal cells. Product development will be carried for volume-production and interfacing with standard imaging equipment. Custom software for data recording, analysis and storage will be developed. This product has already received enthusiastic recommendation from several potential clients/end- users. A multi-disciplinary (engineering and biology), industry-academic team with substantial expertise has been assembled for the execution of this challenging project. The developed device will have critical applications both in basic research, where it can be used to characterize and develop next generation delivery vehicles, and in drug discovery where it can be used to study the efficacy of the drug in realistic tumor microvascular networks. The product will be commercialized to pharmaceutical/biotech firms, drug research labs and universities/non-profit centers engaged in cancer research and drug delivery. PUBLIC HEALTH RELEVANCE: The developed device will have critical applications both in basic research, where it can be used to characterize and develop next generation delivery vehicles, and in drug discovery where it can be used to study the efficacy of the drug in these realistic tumor microvascular networks. The product will be commercialized to pharmaceutical/biotech firms, drug research labs and universities/non-profit centers engaged in cancer research and drug delivery.